Influence of parameter accuracy on pharmacokinetic analysis of hyperpolarized pyruvate

PurposeTo explore the effects of noise and error on kinetic analyses of tumor metabolism using hyperpolarized [1-C-13] pyruvate. MethodsNumerical simulations were performed to systematically investigate the effects of noise, the number of unknowns, and error in kinetic parameter estimates on kinetic analysis of the apparent rate of chemical conversion from hyperpolarized pyruvate to lactate (k(PL)). A pharmacokinetic model with two physical and two chemical pools of hyperpolarized spins was used to generate and analyze the synthetic data. ResultsThe reproducibility of k(PL) estimates worsened quickly when peak signal-to-noise ratio for hyperpolarized pyruvate was below approximately 20. The accuracy of k(PL) estimates was most sensitive to errors in high excitation angles, the vascular blood volume fraction (v(b)), and the rate of pyruvate extravasation (k(ve)), and was least sensitive to errors in the T-1 of pyruvate. When v(b) and/or k(ve) were fit as additional unknowns, the accuracy of k(PL) estimates suffered, and when the vascular input function of pyruvate was also fit, the reproducibility of k(PL) estimates worsened. ConclusionsThe accuracy and precision of k(PL) estimates improve substantially for peak signal-to-noise ratio above approximately 20. Accurate estimates of perfusion parameters (combinations of v(b), k(ve), and the pyruvate vascular input function) and transmit calibration at high excitation angles have the greatest effect on the accuracy of kinetic analyses. Magn Reson Med 79:3239-3248, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.